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Transcript
DNAi Site Guide
1
DNAi Site Guide
Timeline
Pre 1920’s
Johann Gregor Mendel, Friedrich Miescher, Carl Erich Correns, Hugo De Vries, Erich Von TschermakSeysenegg, Thomas Hunt Morgan
1920-49
Hermann Muller, Barbara McClintock, George Wells Beadle, Edward Lawrie Tatum, Joshua
Lederberg, Oswald Theodore Avery
1950-54
Erwin Chargaff, Rosalind Elsie Franklin, Martha Chase, Alfred Day Hershey, Linus Pauling, James
Dewey Watson, Francis Harry Compton Crick, Seymour Benzer
1955-59
Francis Harry Compton Crick, Paul Charles Zamecnik, Mahlon Hoagland,
Matthew Stanley Meselson, Franklin William Stahl, Arthur Kornberg
1960’s
Sydney Brenner, Marshall Warren Nirenberg, François Jacob, Jacques Lucien Monod, Roy John
Britten
1970’s
David Baltimore, Howard Martin Temin, Stanley Norman Cohen, Herbert W. Boyer, Richard John
Roberts, Phillip Allen Sharp, Roger Kornberg, Frederick Sanger
1980’s
Christiane Nüsslein-Volhard, Eric Francis Wieschaus, Kary Mullis, Thomas Robert Cech, Sidney
Altman, Mario Renato Capecchi
1990-2000
Mary-Claire King, Stephen P.A. Fodor, Patrick Henry Brown, John Craig Venter
Francis Collins, John Sulston
Code
Finding the structure
Problem
What is the structure of DNA?
DNAi Site Guide 2
Players
Erwin Chargaff, Rosalind Franklin, Linus Pauling,
James Watson and Francis Crick, Maurice Wilkins
Pieces of the puzzle
Wilkins' X-ray, Pauling's triple helix, Franklin's X-ray,
Watson's base pairing, Chargaff's ratios
Putting it together
DNA is a double-stranded helix.
Copying the code
Problem
How is DNA copied?
Players
James Watson and Francis Crick, Sydney Brenner,
François Jacob, Matthew Meselson, Arthur Kornberg
Pieces of the puzzle
The Central Dogma, Semi-conservative replication
Models of DNA replication, The RNA experiment, DNA synthesis
Putting it together
DNA is used as a template for copying information.
Reading the code
Problem
How is the DNA code read?
Players
Paul Zamecnik and Mahlon Hoagland, Sydney Brenner, Marshall Nirenberg, Marshall
Nirenberg and collaborators, Har Gobind Khorana
Pieces of the puzzle
Breaking the code, Cell-free extracts, The genetic code, The other codons, Defining the gene
Putting it together
The DNA code is read in triplets.
DNAi Site Guide 3
Controlling the code
Problem
How is the DNA code controlled?
Players
François Jacob and Jacques Monod, Walter Gilbert
Pieces of the puzzle
DNA packaging, The lac operon
Putting it together
The DNA code is regulated by proteins
Manipulation
Revolution
Problem
How do you study a gene?
Players
James Watson, Paul Berg, Herbert Boyer and Stanley Cohen, The controversy
Pieces of the puzzle
Restriction enzymes, DNA ligation, The first recombinant DNA, DNA transformation
Putting it together
rDNA: more risk than reward?
Techniques
Cutting & pasting
Using enzymes to manipulate DNA
Sorting & sequencing
Delivering foreign DNA into a cell
Transferring & storing
Analyzing the activity of thousands of genes
Amplifying
Determining the size and sequence of DNA fragments
DNAi Site Guide 4
Large-scale analysis
Making many copies of DNA
Model organisms
Using model organisms in research
Production
Problem
Making insulin with recombinant DNA technology
Players
Herbert Boyer, David Goeddel, Walter Gilbert
Pieces of the puzzle
Synthetic insulin, Synthesizing the DNA, Isolating the DNA, The P4 facility
Putting it together
Synthetic insulin was made using recombinant DNA.
Genome
Tour
Flyover
The landscape of a chromosome
Chromosome close-up
Chromosome coiling and contents
Genome FISHing
FISH for information about your chromosomes: Centromeres, Telomeres, Variation
Genome spots
Click on a "spot" to find out about the gene or genes at that location
The Project
Problem
How do you map, sequence, and find all the genes in the human genome?
Players
Pros & cons, Public consortium, Private project, Money, Technology, Competition and the
media
DNAi Site Guide 5
Pieces of the puzzle
Maps and markers, Storing DNA, Sequencing head to toe, Whole genome shotgun, Sequencing
DNA, Dealing with the data, Finding genes
Putting it together
Viewing our code for the first time
Genome Mining
Meaning
Meaningful sequences
DNA analysis
Analyzing DNA
Gene features
What makes up a gene?
Gene finding
Finding genes in DNA
Gene Boy
A multi-function sequence analysis tool
Applications
Human identification
Fingerprint
DNA variations and fingerprints, The first DNA fingerprints, Today's DNA profile
Case study 1
Sarbah vs. Home Office, Ghana Immigration Case, 1985
Case study 2
State of Florida vs. Jones and Reesh, Murder at Rodman Dam, 1988
Case study 3
The Innocence Project
DNAi Site Guide 6
Recovering the Romanovs
The Romanov family
The history of the Romanovs, the last Imperial family of Tsarist Russia
The mystery of Anna Anderson
Anna Anderson claimed to be Anastasia, the missing Anastasia Romanov
Science solves a mystery
DNA science was used to determine whether Anna Anderson was Anastasia
Genes and medicine
Gene hunting
Mary-Claire King, Mark Skolnick, Markers, The finish line
Gene testing
Barbara Weber, Denise, Making a pedigree, Testing
Genetic profiling
Patrick (Pat) Brown, Stephen Fodor, David Botstein, Techniques
Drug design
Brian Druker, The Philadelphia chromosome, Bud's story, How Gleevec™ works
Gene targeting
Mario Capecchi, Animal models, Techniques, Possibilities
Human origins
Our family tree
Meet the extended family
Comparisons
Bones, Behavior, DNA
Gene genealogy
Mitochondrial DNA, Y Chromosome, Other genome regions,
A molecular clock?, Tracing ancestries
Migrations
Follow the paths, Hear the stories
DNAi Site Guide 7
Variation
Primate diversity, Interviews, Variation activity
Chronicle
Threat of the Unfit
Founders
Bringing the eugenics movement to prominence
The fit and unfit
Pedigrees of the fit and unfit
Threats
The eugenicists' views on the socially "unfit"
Epilogue
Eugenics as the "solution" to social problems
Trial of Carrie Buck
Prologue
Upholding the "legality" of sterilization
Players
Carrie Buck, Emma Buck, Vivian Dobbs, Albert Priddy, Aubrey Strode, Irving Whitehead,
Arthur Estabrook, Harry Laughlin, Oliver Wendell Holmes
Trials
Buck vs. Bell: forced sterilization of the "feebleminded"
Outcome
The Supreme Court decision
Epilogue
The truth about Buck vs. Bell
In the Third Reich
Taking the torch
Nazi eugenics
The final solution
"The final solution" to mental illness
DNAi Site Guide 8
Applying the solution
The concentration camps
Epilogue
After World War II
Living with Eugenics
Living with depression
The highs and lows of manic depression
Kallikak revisited
Comparing family pedigrees
The diagnosis
Dealing with the diagnosis
Eplilogue
The "eugenic quandary," prenatal testing for manic depression